Co-Administration of LDX (SPD489) and Venlafaxine XR (EFFEXOR XR) in Healthy Volunteers

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01235338
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.7
• Patients Per Site Per Month: 30.1

Study Details

Study Description

Brief Summary

This study will examine the effects of co-administration of SPD489 and the antidepressant EFFEXOR XR on the pharmacokinetics of lisdexamfetamine, d-amphetamine, and EFFEXOR XR. In addition, serial blood pressure and pulse measures will be obtained and examined to ensure that there are no unexpected changes in vital signs following co administration of SPD489 and EFFEXOR XR that would impact the further study of this drug combination. The hypothesis is that a drug drug interaction could possibly exist.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: LDX + Venlafaxine XR; Drug: Venlafaxine XR + LDX	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-label, Drug Interaction Study Evaluating the Pharmacokinetic Profiles of SPD489 and EFFEXOR XR, Administered Alone and in Combination in Healthy Adult Subjects
• Actual Study Start Date: Oct 28, 2010
• Actual Primary Completion Date: Dec 30, 2010
• Actual Study Completion Date: Jan 17, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LDX (SPD489) + Venlafaxine XR (Effexor XR)	Drug: LDX + Venlafaxine XR; Day 1-5 LDX 30mg Day 6-10 LDX 50mg Day 11-15 LDX 70mg Day 16-20 LDX 70mg and Venlafaxine XR 75mg daily Day 21-25 LDX 70mg and Venlafaxine XR 150mg daily Day 26-30 LDX 70mg and Venlafaxine XR 225mg daily Day 31-34 Venlafaxine XR 150mg daily Day 35-38 Venlafaxine XR 75mg daily.; Other Names: Lisdexamfetamine dimesylate, LDX, Vyvanse, SPD489; Venlafaxine hydrochloride extended-release, Effexor XR,
Experimental: Venlafaxine XR + LDX	Drug: Venlafaxine XR + LDX; Day 1-5 Venlafaxine XR 75mg Day 6-10 Venlafaxine XR 150mg Day 11-15 Venlafaxine XR 225mg Day 16-20 Venlafaxine XR 225mg and LDX 30mg daily Day 21-25 Venlafaxine XR and LDX 50mg daily Day 26-30 Venlafaxine XR 225mg and LDX 70mg daily Day 31-34 Venlafaxine XR 150mg Day 35-38 Venlafaxine XR 75mg.; Other Names: Venlafaxine hydrochloride extended-release, Effexor XR; Lisdexamfetamine dimesylate, LDX, Vyvanse, SPD489

Outcome Measures

Primary Outcome Measures

1. Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate [Day 15 and Day 30 (24 hour sampling)]

   Lisdexamfetamine dimesylate (SPD489) itself is inactive, but following oral administration is converted to the active isomer, d-amphetamine, that is responsible for the drug's therapeutic activity.

2. Cmax of d-Amphetamine [Day 15 and Day 30 (24 hour sampling)]

   d-Amphetamine is the active isomer of Lisdexamfetamine dimesylate (SPD489) and is responsible for the drug's therapeutic activity.

3. Cmax of Venlafaxine Hydrochloride [Day 15 and Day 30 (24 hour sampling)]

   Venlafaxine Hydrochloride is the active ingredient of Effexor XR

4. Cmax of o-Desmethylvenlafaxine [Day 15 and Day 30 (24 hour sampling)]

   Venlafaxine, after oral administration, is metabolized in the liver to an active metabolite, o-Desmethylvenlafaxine.

5. Cmax of Composite (Venlafaxine + o-Desmethylvenlafaxine) [Day 15 and Day 30 (24 hour sampling)]

6. Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate [Day 15 and Day 30 (24 hour sampling)]

7. AUC of d-Amphetamine [Day 15 and Day 30 (24 hour sampling)]

8. AUC of Venlafaxine Hydrochloride [Day 15 and Day 30 (24 hour sampling)]

9. AUC of o-Desmethylvenlafaxine [Day 15 and Day 30 (24 hour sampling)]

10. AUC of Composite (Venlafaxine + o-Desmethylvenlafaxine) [Day 15 and Day 30 (24 hour sampling)]

11. Time of Maximum Plasma Concentration (Tmax) of Lisdexamfetamine Dimesylate [Day 15 and Day 30 (24 hour sampling)]

12. Tmax of d-Amphetamine [Day 15 and Day 30 (24 hour sampling)]

13. Tmax of Venlafaxine Hydrochloride [Day 15 and Day 30 (24 hour sampling)]

14. Tmax of o-Desmethylvenlafaxine [Day 15 and Day 30 (24 hour sampling)]

15. Tmax of Composite (Venlafaxine + o-Desmethylvenlafaxine) [Day 15 and Day 30 (24 hour sampling)]

Secondary Outcome Measures

1. Systolic Blood Pressure [Baseline and up to 39 days]

2. Diastolic Blood Pressure [Baseline and up to 39 days]

3. Pulse Rate [Baseline and up to 39 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Age 18-45 years

2. Subject is willing to comply with any applicable contraceptive requirements of the protocol and is:

• Male, or

• Non-pregnant, non-lactating female

• Females must be at least 90 days post partum or nulliparous.

1. Female subjects must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test

2. Satisfactory medical assessment

3. Ability to provide information on family history of hypertension.

4. Body Mass Index (BMI) between 18.5 and 30.0kg/m² inclusive.

5. Ability to swallow all investigational products.

Exclusion Criteria:

1. Current or recurrent disease (e.g., cardiovascular, renal, liver, gastrointestinal, malignancy or other conditions)

2. Current or relevant previous history of physical or psychiatric illness.

3. Significant illness.

4. History of significant anxiety, tension, or agitation as assessed by the Investigator.

5. History of or current diagnosis of glaucoma.

6. History of a seizure disorder (other than infantile febrile seizures), any tic disorder or a current diagnosis and/or known family history of Tourette's Disorder.

7. History of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, transient ischemic attack or stroke, or other serious cardiac problems.

8. History of controlled or uncontrolled hypertension or a resting sitting systolic BP

139mmHg or diastolic BP >89mmHg.

1. Known family history of sudden cardiac death or ventricular arrhythmia.

2. Suicidal ideation or any lifetime history of suicidal behavior.

3. Consumption of alcohol, Seville oranges, grapefruit, or any grapefruit containing products within 7 days of first dose of investigational product.

4. Current use of any medication (including prescription, over the counter [OTC], herbal or homeopathic preparations or supplements) with the exception of the occasional dose of acetaminophen, or hormonal contraceptives.

5. History of alcohol or other substance abuse within the last year.

6. A positive screen for alcohol or drugs of abuse.

7. Male subjects who consume more than 21 units of alcohol per week or 3 units per day. Female subjects who consume more than 14 units of alcohol per week or 2 units per day. [1 alcohol unit =1 beer = 1 wine (5oz) = 1 liquor (1.5oz) = 0.75oz alcohol]

8. A positive human immunodeficiency virus (HIV) antibody screen, Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody screen.

9. Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g. gum, patch). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product.

10. Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. (One caffeine unit is contained in the following items: one 6oz. cup of coffee, two 12oz. cans of cola, one 12oz. cup of tea, three 1oz. chocolate bars, or one 8oz. serving of an energy drink. Decaffeinated coffee, tea, or cola are not considered to contain caffeine).

11. Donation of blood or blood products (e.g., plasma or platelets) within 60 days prior to receiving the first dose of investigational product.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Pharmacology of Miami	Miami	Florida	United States	33014

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• FDA Recall Information
• FDA-approved label

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01235338
• Other Study ID Numbers: SPD489-117
• First Posted: Nov 5, 2010
• Last Update Posted: Jun 14, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Lisdexamfetamine Dimesylate; Venlafaxine Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	Of the 80 randomized subjects, 3 did not receive any investigational product and therefore were not included in the Safety Analysis/Pharmacokinetic Analysis Sets (n = 77).

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Period Title: Overall Study
STARTED	42	38
COMPLETED	31	33
NOT COMPLETED	11	5

Baseline Characteristics

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX	Total
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Total of all reporting groups
Overall Participants	40	37	77
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.2 (7.01)	33.8 (7.29)	33.5 (7.10)
Age, Customized (Count of Participants)
Between 18 and 45 years	40 100%	37 100%	77 100%
Sex: Female, Male (Count of Participants)
Female	12 30%	10 27%	22 28.6%
Male	28 70%	27 73%	55 71.4%
Region of Enrollment (Count of Participants)
United States	40 100%	37 100%	77 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate
Description	Lisdexamfetamine dimesylate (SPD489) itself is inactive, but following oral administration is converted to the active isomer, d-amphetamine, that is responsible for the drug's therapeutic activity.
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set (PAS) defined as all subjects who took a t least 1 dose of investigational product and had at least 1 post-dose safety assessment and who had no major deviations related to investigational product intake (e.g. vomiting) and for whom the primary pharmacokinetic data were considered sufficient and interpretable.

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	49.06 (32.25)	0 (0)
Day 30	49.84 (34.3)	50.77 (19.68)

2. Primary Outcome

Title	Cmax of d-Amphetamine
Description	d-Amphetamine is the active isomer of Lisdexamfetamine dimesylate (SPD489) and is responsible for the drug's therapeutic activity.
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	88.91 (26.87)	0 (0)
Day 30	88.91 (22.72)	85.27 (20.55)

3. Primary Outcome

Title	Cmax of Venlafaxine Hydrochloride
Description	Venlafaxine Hydrochloride is the active ingredient of Effexor XR
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	0 (0)	210.98 (120.6)
Day 30	198.5 (105.48)	228.89 (124.42)

4. Secondary Outcome

Title	Systolic Blood Pressure
Time Frame	Baseline and up to 39 days

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (SAS) defined as all enrolled subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	40	37
Baseline	110.17 (8.996)	110.48 (9.623)
Up to 39 Days	117.82 (8.547)	121.51 (7.695)

5. Secondary Outcome

Title	Diastolic Blood Pressure
Time Frame	Baseline and up to 39 days

Outcome Measure Data

Analysis Population Description

SAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	40	37
Baseline	73.69 (7.446)	73.68 (6.730)
Up to 39 Days	77.85 (6.628)	80.45 (7.4515)

6. Primary Outcome

Title	Cmax of o-Desmethylvenlafaxine
Description	Venlafaxine, after oral administration, is metabolized in the liver to an active metabolite, o-Desmethylvenlafaxine.
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	0 (0)	420.55 (139.67)
Day 30	413.71 (149.97)	371.54 (104.92)

7. Primary Outcome

Title	Cmax of Composite (Venlafaxine + o-Desmethylvenlafaxine)
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	0 (0)	624.56 (179.7)
Day 30	603.49 (181.32)	588.68 (158.79)

8. Primary Outcome

Title	Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	65.5 (44.0)	0 (0)
Day 30	63.9 (43.7)	60.8 (19.2)

9. Primary Outcome

Title	AUC of d-Amphetamine
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	1143.4 (292.8)	0 (0)
Day 30	1135.4 (301.5)	1049.2 (268.7)

10. Primary Outcome

Title	AUC of Venlafaxine Hydrochloride
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	0 (0)	2900.0 (1919.3)
Day 30	2839.7 (1706.8)	3202.6 (1942.5)

11. Primary Outcome

Title	AUC of o-Desmethylvenlafaxine
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	0 (0)	8363.3 (2168.1)
Day 30	8061.3 (2868.7)	6955.1 (1962.8)

12. Primary Outcome

Title	AUC of Composite (Venlafaxine + o-Desmethylvenlafaxine)
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	0 (0)	10738.0 (3273.3)
Day 30	10673.9 (3035.7)	10342.2 (3096.1)

13. Primary Outcome

Title	Time of Maximum Plasma Concentration (Tmax) of Lisdexamfetamine Dimesylate
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	1.1 (0.3)	0 (0)
Day 30	1.1 (0.3)	1.0 (0.3)

14. Primary Outcome

Title	Tmax of d-Amphetamine
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	3.5 (1.5)	0 (0)
Day 30	3.2 (1.0)	3.1 (1.3)

15. Primary Outcome

Title	Tmax of Venlafaxine Hydrochloride
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	0 (0)	6.4 (0.8)
Day 30	6.0 (1.3)	5.9 (0.6)

16. Primary Outcome

Title	Tmax of o-Desmethylvenlafaxine
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	0 (0)	7.9 (1.2)
Day 30	8.5 (1.7)	7.9 (1.3)

17. Primary Outcome

Title	Tmax of Composite (Venlafaxine + o-Desmethylvenlafaxine)
Time Frame	Day 15 and Day 30 (24 hour sampling)

Outcome Measure Data

Analysis Population Description

PAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	32	34
Day 15	0 (0)	7.3 (1.1)
Day 30	7.1 (1.4)	7.0 (1.2)

18. Secondary Outcome

Title	Pulse Rate
Time Frame	Baseline and up to 39 days

Outcome Measure Data

Analysis Population Description

SAS

Arm/Group Title	LDX + Venlafaxine XR	Venlafaxine XR + LDX
Arm/Group Description	LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg once daily (QD) Days 1-5, then LDX 50 mg QD Days 6-10, then LDX 70 mg QD Days 11-15, then LDX 70 mg + venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 16-20, then LDX 70 mg + venlafaxine XR 150 mg QD Days 21-25, then LDX 70 mg + venlafaxine XR 225 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.	Venlafaxine XR (Venlafaxine Hydrochloride extended-release, Effexor® XR) 75 mg QD Days 1-5, then venlafaxine XR 150 mg QD Days 6-10, then venlafaxine XR 225 mg QD Days 11-15, then venlafaxine XR 225 mg + LDX (Lisdexamfetamine Dimesylate, SPD489, Vyvanse®) 30 mg QD Days 16-20, then venlafaxine XR 225 mg + LDX 50 mg QD Days 21-25, then venlafaxine XR 225 mg + LDX 70 mg QD Days 26-30, then venlafaxine XR 150 mg QD Days 31-34, then venlafaxine XR 75 mg QD Days 35-38.
Measure Participants	40	37
Baseline	66.24 (7.940)	66.55 (10.318)
Up to 39 Days	77.47 (8.621)	81.72 (7.068)

Adverse Events

Arm/Group Title	LDX (SPD489)		LDX + Venlafaxine XR/Venlafaxine XR + LDX		Venlafaxine XR Titration		Venlafaxine XR Tapering
Arm/Group Description	Titration dosing period		Combination dosing periods		Titration dosing period (Effexor XR 75, 150, and 225 mg)		Tapering dosing period (Effexor XR 150 and 75 mg)
All Cause Mortality
	LDX (SPD489)		LDX + Venlafaxine XR/Venlafaxine XR + LDX		Venlafaxine XR Titration		Venlafaxine XR Tapering
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LDX (SPD489)		LDX + Venlafaxine XR/Venlafaxine XR + LDX		Venlafaxine XR Titration		Venlafaxine XR Tapering
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/40 (2.5%)		0/67 (0%)		0/37 (0%)		0/67 (0%)
Nervous system disorders
Presyncope	1/40 (2.5%)	1	0/67 (0%)	0	0/37 (0%)	0	0/67 (0%)	0
Other (Not Including Serious) Adverse Events
	LDX (SPD489)		LDX + Venlafaxine XR/Venlafaxine XR + LDX		Venlafaxine XR Titration		Venlafaxine XR Tapering
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/40 (82.5%)		46/67 (68.7%)		25/37 (67.6%)		20/67 (29.9%)
Cardiac disorders
Palpitations	8/40 (20%)	11	2/67 (3%)	3	0/37 (0%)	0	0/67 (0%)	0
Eye disorders
Vision Blurred	2/40 (5%)	2	0/67 (0%)	0	0/37 (0%)	0	0/67 (0%)	0
Gastrointestinal disorders
Constipation	3/40 (7.5%)	3	11/67 (16.4%)	14	3/37 (8.1%)	3	0/67 (0%)	0
Diarrhea	2/40 (5%)	3	2/67 (3%)	2	3/37 (8.1%)	3	2/67 (3%)	2
Dry Mouth	10/40 (25%)	13	6/67 (9%)	6	7/37 (18.9%)	8	0/67 (0%)	0
Nausea	6/40 (15%)	7	4/67 (6%)	4	7/37 (18.9%)	9	6/67 (9%)	7
Stomach Discomfort	2/40 (5%)	2	0/67 (0%)	0	0/37 (0%)	0	0/67 (0%)	0
General disorders
Chest Pain	3/40 (7.5%)	3	1/67 (1.5%)	1	0/37 (0%)	0	0/67 (0%)	0
Metabolism and nutrition disorders
Anorexia	12/40 (30%)	21	0/67 (0%)	0	9/37 (24.3%)	10	0/67 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	2/40 (5%)	2	0/67 (0%)	0	0/37 (0%)	0	0/67 (0%)	0
Nervous system disorders
Dizziness	3/40 (7.5%)	3	7/67 (10.4%)	9	4/37 (10.8%)	5	7/67 (10.4%)	7
Headache	7/40 (17.5%)	8	13/67 (19.4%)	17	6/37 (16.2%)	6	3/67 (4.5%)	3
Somnolence	7/40 (17.5%)	7	0/67 (0%)	0	7/37 (18.9%)	7	3/67 (4.5%)	3
Psychiatric disorders
Anxiety	5/40 (12.5%)	7	2/67 (3%)	2	0/37 (0%)	0	0/67 (0%)	0
Euphoric Mood	3/40 (7.5%)	4	0/67 (0%)	0	0/37 (0%)	0	0/67 (0%)	0
Insomnia	7/40 (17.5%)	7	5/67 (7.5%)	6	3/37 (8.1%)	5	0/67 (0%)	0
Libido Decreased	0/40 (0%)	0	0/67 (0%)	0	2/37 (5.4%)	2	0/67 (0%)	0
Renal and urinary disorders
Urinary Hesitation	0/40 (0%)	0	5/67 (7.5%)	5	0/37 (0%)	0	0/67 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/40 (5%)	2	1/67 (1.5%)	1	0/37 (0%)	0	0/67 (0%)	0
Epistaxis	0/40 (0%)	0	5/67 (7.5%)	5	0/37 (0%)	0	0/67 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.